Amniotic fluid‐derived small extracellular vesicles for predicting postnatal severe outcome of congenital diaphragmatic hernia

Author:

Matsuo Seiko1,Yokoi Akira123ORCID,Yoshida Kosuke12,Kitagawa Masami1,Asano‐Inami Eri1,Miura Mayo4,Yasui Takao567,Tano Sho1,Ushida Takafumi18,Imai Kenji1,Kajiyama Hiroaki1,Kotani Tomomi18

Affiliation:

1. Department of Obstetrics and Gynecology Nagoya University Graduate School of Medicine Nagoya Japan

2. Nagoya University Institute for Advanced Research Nagoya Japan

3. Japan Science and Technology Agency (JST) FOREST Kawaguchi Japan

4. Department of Obstetrics and Gynecology Tokoname Municipal Hospital Tokoname Japan

5. Department of Life Science and Technology Tokyo Institute of Technology Yokohama Japan

6. Institute of Nano‐Life Systems, Institutes of Innovation for Future Society Nagoya University Nagoya Japan

7. Department of Biomolecular Engineering, Graduate School of Engineering Nagoya University Nagoya Japan

8. Division of Reproduction and Perinatology, Center for Maternal‐Neonatal Care Nagoya University Hospital Nagoya Japan

Abstract

AbstractCongenital diaphragmatic hernia (CDH) is a life‐threatening condition with high morbidity and mortality rates. The survival rate of neonates with severe CDH is reportedly only 10%–15%. However, prenatal prediction of severe cases is difficult, and the discovery of new predictive markers is an urgent issue. In this study, we focused on microRNAs (miRNAs) in amniotic fluid‐derived small EVs (AF‐sEVs). We identified four miRNAs (hsa‐miR‐127‐3p, hsa‐miR‐363‐3p, hsa‐miR‐493‐5p, and hsa‐miR‐615‐3p) with AUC > 0.8 to classify good prognosis group and poor prognosis group in human study. The AUC for hsa‐miR‐127‐3p and hsa‐miR‐615‐3p, for predicting the poor prognosis, were 0.93 and 0.91, respectively. In addition, in the in vivo study, the miRNA profiles of the lung tissues of CDH rats were different from those of control rats. Additionally, two elevated miRNAs (rno‐miR‐215‐5p and rno‐miR‐148a‐3p) in the lung tissues of CDH rats were increased in the AF‐sEVs of CDH rats. Our results suggest that severe CDH neonates can be predicted prenatally with high accuracy using miRNAs contained in AF‐sEVs. Furthermore, miRNA profile changes in AF‐sEVs reflected the lung status in CDH. Our findings may contribute to the development of advanced perinatal care for patients with CDH.

Funder

Japan Society for the Promotion of Science

Publisher

Wiley

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